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In recent years, exopoly saccharides (EPS) produced by microorganisms have garnered attention due to their functional properties such as improving food quality, regulating intestinal microbiota, antioxidative effects, anticancer properties, immunoprevention, and treatment of cardiovascular diseases. Currently, research on microbial EPS (extracellular polymeric substances) in China is still in its early stages and requires further exploration. This paper comprehensively reviewed the latest advancements in the classification, biosynthesis, structural modification, functional properties, and applications of EPS produced by microorganisms both domestically and internationally. This study also focused on analyzing the biosynthetic pathways and structural features of different types of EPS, as well as the strategies for functional modification through physical, chemical, and biological methods. The aim is to provide new references and guidance for research and development in relevant fields, thereby promoting the application and industrialization of EPS in the food, pharmaceutical, and industrial sectors.

Abstract Background Pruning is an important cultivation management option that has important effects on peach yield and quality. However, the effects of pruning on the overall genetic and metabolic changes in peach leaves and fruits are poorly understood. Results The transcriptomic and metabolomic profiles of leaves and fruits from trees subjected to pruning and unpruning treatments were measured. A total of 20,633 genes and 622 metabolites were detected. Compared with those in the control, 1,127 differentially expressed genes (DEGs) and 77 differentially expressed metabolites (DEMs) were identified in leaves from pruned and unpruned trees (pdLvsupdL), whereas 423 DEGs and 29 DEMs were identified in fruits from the pairwise comparison pdFvsupdF. The content of three auxin analogues was upregulated in the leaves of pruned trees, the content of all flavonoids detected in the leaves decreased, and the expression of almost all genes involved in the flavonoid biosynthesis pathway decreased. The phenolic acid and amino acid metabolites detected in fruits from pruned trees were downregulated, and all terpenoids were upregulated. The correlation analysis revealed that DEGs and DEMs in leaves were enriched in tryptophan metabolism, auxin signal transduction, and flavonoid biosynthesis. DEGs and DEMs in fruits were enriched in flavonoid and phenylpropanoid biosynthesis, as well as L-glutamic acid biosynthesis. Conclusions Pruning has different effects on the leaves and fruits of peach trees, affecting mainly the secondary metabolism and hormone signalling pathways in leaves and amino acid biosynthesis in fruits.

Abstract Developing skeletal editing tools is not a trivial task, and realizing the corresponding single-atom transmutation in a ring system without altering the ring size is even more challenging. Here, we introduce a skeletal editing strategy that enables polycyclic arenols, a highly prevalent motif in bioactive molecules, to be readily converted into N-heteroarenes through carbon–nitrogen transmutation. The reaction features selective nitrogen insertion into the C–C bond of the arenol frameworks by azidative dearomatization and aryl migration, followed by ring-opening, and ring-closing (ANRORC) to achieve carbon-to-nitrogen transmutation in the aromatic framework of the arenol. Using widely available arenols as N-heteroarene precursors, this alternative approach allows the streamlined assembly of complex polycyclic heteroaromatics with broad functional group tolerance. Finally, pertinent transformations of the products, including synthesis complex biheteroarene skeletons, were conducted and exhibited significant potential in materials chemistry.

AbstractPurpose It is unknown whether febuxostat can delay the progression of kidney dysfunction and reduce kidney endpoint events. The aim was to evaluate the renoprotective effect of febuxostat in patients with hyperuricemia or gout by performing a meta-analysis of randomized controlled trials (RCTs).Methods MEDLINE, Web of science, EMBASE, ClinicalTrials.gov, and the Cochrane Central Register for Randomized Controlled Trials were searched. The main outcomes included kidney events (serum creatinine doubling or progression to end-stage kidney disease or dialysis). The secondary outcomes were the rate of change in the estimated glomerular filtration rate (eGFR) and changes in the urine protein or urine albumin to creatinine ratio from baseline to the end of follow-up. We used random-effects models to calculate the pooled risk estimates and 95% CIs.Results A total of 16 RCTs were included in the meta-analysis. In comparison with the control group, the patients who received febuxostat showed a reduced risk of kidney events (RR = 0.56, 95% CI 0.37–0.84, p = 0.006) and a slower decline in eGFR (WMD = 0.90 mL/min/1.73 m2, 95% CI 0.31–1.48, p = 0.003). The pooled results also revealed that febuxostat use reduced the urine albumin to creatinine ratio (SMD = −0.21, 95% CI −0.41 to −0.01, p = 0.042).Conclusion Febuxostat use is associated with a reduced risk of kidney events and a slow decline in eGFR. In addition, the urine albumin to creatinine ratio decreased in febuxostat users. Accordingly, it is an effective drug for delaying the progression of kidney function deterioration in patients with gout.Systematic review registration: PROSPERO CRD42021272591

Abstract Autism spectrum disorder (ASD) is a neurodevelopmental disorder, characterized by social communication disability and stereotypic behavior. This study aims to investigate the impact of prenatal exposure to 1‐nitropyrene (1‐NP), a key component of motor vehicle exhaust, on autism‐like behaviors in a mouse model. Three‐chamber test finds that prenatal 1‐NP exposure causes autism‐like behaviors during the weaning period. Patch clamp shows that inhibitory synaptic transmission is reduced in medial prefrontal cortex of 1‐NP‐exposed weaning pups. Immunofluorescence finds that prenatal 1‐NP exposure reduces the number of prefrontal glutamate decarboxylase 67 (GAD67) positive interneurons in fetuses and weaning pups. Moreover, prenatal 1‐NP exposure retards tangential migration of GAD67‐positive interneurons and downregulates interneuron migration‐related genes, such as Nrg1, Erbb4, and Sema3F, in fetal forebrain. Mechanistically, prenatal 1‐NP exposure reduces hydroxymethylation of interneuron migration‐related genes through inhibiting ten‐eleven translocation (TET) activity in fetal forebrain. Supplement with alpha‐ketoglutarate (α‐KG), a cofactor of TET enzyme, reverses 1‐NP‐induced hypohydroxymethylation at specific sites of interneuron migration‐related genes. Moreover, α‐KG supplement alleviates 1‐NP‐induced migration retardation of interneurons in fetal forebrain. Finally, maternal α‐KG supplement improves 1‐NP‐induced autism‐like behaviors in weaning offspring. In conclusion, prenatal 1‐NP exposure causes autism‐like behavior partially by altering DNA hydroxymethylation of interneuron migration‐related genes in developing brain.

IntroductionPeach (Prunus persica) has a high nutritional and economic value. However, its overgrowth can lead to yield loss. Regulating the growth of peach trees is challenging. The small auxin-up RNA (SAUR) gene family is the largest family of auxin-responsive genes, which play important roles in plant growth and development. However, members of this gene family are rarely reported in peach.MethodsIn this study, we measured leaf area, chlorophyll and lignin content to detect the role of PpSAUR5 on growth through transgenic Arabidopsis.ResultsPpSAUR5 responds to auxin and gibberellin, promoting and inhibiting the synthesis of gibberellin and auxin, respectively. The heterologous transformation of PpSAUR5 in Arabidopsis led to enhanced growth of leaves and siliques, lightening of leaf color, decrease in chlorophyll content, increase in lignin content, abnormalities in the floral organs, and distortion of the inflorescence axis. Transcriptome data analysis of PpSAUR5 overexpression and wild-type lines revealed 854 differentially expressed genes (DEGs). GO and KEGG analyses showed that the DEGs were primarily involved in biological processes, such as cellular processes, metabolic processes, response to stimuli, and catalytic activity. These genes were mainly enriched in pathways, such as phenylalanine biosynthesis, phytohormone signaling, and MAPK signaling.DiscussionIn summary, these results suggested that PpSAUR5 might regulate tree vigor by modulating the synthesis of auxin and gibberellin. Future studies can use PpSAUR5 as a candidate gene to elucidate the potential regulatory mechanisms underlying peach tree vigor.

Nitrate is the main source of nitrogen for plant growth and development under aerobic conditions, which serves as an important nutrient and signaling molecule, understanding the nitrate signaling pathway is important for agricultural production. Auxin response factors (ARFs) are associated with nitrate signaling, but their underlying mechanism is less known in apples. In this study, it was found that MdARF18 can be expressed as a transcription factor activated by nitrate, and inhibited the uptake of nitrate in apples. Then, MdARF18 was found to bind directly to the TGTCTT site of the MdNRT1.1 promoter and significantly reduced its expression. In conclusion, MdARF18 regulates nitrate uptake in plants by mediating the expression of MdNRT1.1, providing insight into the mechanism by which MdARF18 regulates nitrate uptake and utilization in apples.

Abstract Background Microglia-mediated neuroinflammation in Alzheimer’s disease (AD) is not only a response to pathophysiological events, but also plays a causative role in neurodegeneration. Cytoplasmic cysteinyl-tRNA synthetase (CARS) is considered to be a stimulant for immune responses to diseases; however, it remains unknown whether CARS is involved in the pathogenesis of AD. Methods Postmortem human temporal cortical tissues at different Braak stages and AD patient-derived serum samples were used to investigate the changes of CARS levels in AD by immunocytochemical staining, real-time PCR, western blotting and ELISA. After that, C57BL/6J and APP/PS1 transgenic mice and BV-2 cell line were used to explore the role of CARS protein in memory and neuroinflammation, as well as the underlying mechanisms. Finally, the associations of morphological features among CARS protein, microglia and dense-core plaques were examined by immunocytochemical staining. Results A positive correlation was found between aging and the intensity of CARS immunoreactivity in the temporal cortex. Both protein and mRNA levels of CARS were increased in the temporal cortex of AD patients. Immunocytochemical staining revealed increased CARS immunoreactivity in neurons of the temporal cortex in AD patients. Moreover, overexpression of CARS in hippocampal neurons induced and aggravated cognitive dysfunction in C57BL/6J and APP/PS1 mice, respectively, accompanied by activation of microglia and the TLR2/MyD88 signaling pathway as well as upregulation of proinflammatory cytokines. In vitro experiments showed that CARS treatment facilitated the production of proinflammatory cytokines and the activation of the TLR2/MyD88 signaling pathway of BV-2 cells. The accumulation of CARS protein occurred within dense-core Aβ plaques accompanied by recruitment of ameboid microglia. Significant upregulation of TLR2/MyD88 proteins was also observed in the temporal cortex of AD. Conclusions The findings suggest that the neuronal CARS drives neuroinflammation and induces memory deficits, which might be involved in the pathogenesis of AD.

The microstructure of a compressed explosive solid is closely related to its shock sensitivity and mechanical properties. In this study, ultra-small-angle and small-angle X-ray scattering (USAXS and SAXS) techniques were combined to explore the hierarchical microstructure of die-pressed 2,4,6-trinitro-1,3,5-benzenetriamine (TATB) discs obtained from nanostructured TATB (nano-TATB) powder as the precursor. Using the Guinier-Porod model, the pseudo-invariants, and Porod's law, this study analyzed the microstructures of the materials on a nanometer scale to track the changes in void size, porosity, and interfacial area, which reflected the response of TATB under applied pressures of 1, 2, 5, 10, 15 ​kN and 30 ​kN. Results show that there existed three populations of voids in the measured q range. The intergranular voids with sizes of tens of nanometers were sensitive to low pressures (15 ​kN), as indicated by the decrease in the volume fractal dimension. Porosities of the voids with sizes of 1–900 ​nm, which were determined by the pseudo-invariants obtained from the scattering data, decreased from 6% to 1% as the pressures increased from 1 ​kN to 30 ​kN. The response of these structural parameters to external pressures implies that the main densification mechanisms under die compression include the flow, fracturing, and plastic deformation of the TATB granules. This study provides a direct insight into the structural evolution of TATB during compression.

Pneumoconiosis is a common occupational disease that can worsen with accompanying infection. Torque teno virus (TTV) is a prevalent human virus with multiple genotypes that can chronically and persistently infect individuals. However, the prevalence of TTV in pneumoconiosis patients is still unclear. This research aims to detect the presence and prevalence of TTV in the alveolar lavage fluid of pneumoconiosis patients in the Hunan Province of China using PCR. As a result, a 65.5% positive rate (19 out of 29) of TTV was detected. The TTV detection rate varies among different stages of silicosis and different pneumoconiosis patient ages. Nine novel TTV genomes ranging in size from 3719 to 3908 nt, named TTV HNPP1, HNPP2, HNPP3, HNPP4, HNPP5, HNPP6-1, HNPP6-2, HNPP7-1 and HNPP7-2, were identified. A genomic comparison and phylogenetic analysis indicated that these nine TTVs represent five different species with high genetic diversity which belong to the genus Alphatorquevirus. HNPP6-1 and HNPP6-2 belong to TTV3, HNPP5 belongs to TTV13, HNPP1 belongs to TTV24, HNPP4 belongs to TTV20, and the others belong to TTV19. The genomes of TTV HNPP1, HNPP6-1, and HNPP6-2 contain three putative open reading frames (ORFs) coding for proteins, ORF1, ORF2, and ORF3, while the other six TTV genomes contain two ORFs coding for proteins, ORF1 and ORF2. These results provide the first description of TTV epidemiology in pneumoconiosis patients in China. The newly identified TTV genome sequences reveal the high genetic diversity of TTV in pneumoconiosis patients and could contribute to a deeper understanding of TTV retention and infection in humans.

Abstract Aims Exosomes are known as nanovesicles that are naturally secreted, playing an essential role in stem-mediated cardioprotection. This study mainly focused on investigating if exosomes derived from miR-214 overexpressing mesenchymal stem cells (MSCs) show more valid cardioprotective ability in a rat model of acute myocardial infarction (AMI) and its potential mechanisms. Methods Exosomes were isolated from control MSCs (Ctrl-Exo) and miR-214 overexpressing MSCs (miR-214OE-Exo) and then they were delivered to cardiomyocytes and endothelial cells in vitro under hypoxia and serum deprivation (H/SD) condition or in vivo in an acutely infarcted Sprague-Dawley rat heart. Regulated genes and signal pathways by miR-214OE-Exo treatment were explored using western blot analysis and luciferase assay. Results in vitro , miR-214OE-Exo enhanced migration, tube-like formation in endothelial cells. In addition, miR-214OE-Exo ameliorated the survival of cardiomyocytes under H/SD. In the rat AMI model, compared to Ctrl-Exo, miR-214OE-Exo reduced myocardial apoptosis, and therefore reduced infarct size and improved cardiac function. Besides, miR-214OE-Exo accelerated angiogenesis in peri-infarct region. Mechanistically, we identified that exosomal miR-214-3p promoted cardiac repair via targeting PTEN and activating p-AKT signal pathway. Conclusion Exosomes derived from miR-214 overexpressing MSCs have greatly strengthened the therapeutic efficacy for treatment of AMI by promoting cardiomyocyte survival and endothelial cell function. Graphical abstract

Abstract Objective To investigate the relationship between infant feeding practices and autism spectrum disorder (ASD) among children aged 2–5 years in the United States (US). Methods Data from the 2016–2020 National Survey of Children’s Health, a nationally representative cross-sectional survey, were utilized for this study. Questionnaires were administered to parents of children aged 2–5 years to gather information on ASD diagnosis, infant feeding practices, and demographic factors (e.g., child sex, ethnic group, and maternal age at birth). Logistic regression with sample weights was employed to assess the association between infant feeding practices and ASD, while controlling for demographic variables. Polynomial regression models were used to examine trends in exclusive breastfeeding and ever breastfeeding rates among children with and without ASD. Results A total of 35,050 children aged 2–5 years were analyzed, including 616 diagnosed with ASD, after excluding participants with missing information on breastfeeding and ASD diagnosis. Of these children with ASD, 76.6% (n = 472) had a breastfeeding history, with 66.6% (n = 410) engaged in partial breastfeeding and 10.1% (n = 62) exclusively breastfed. Adjusted odds ratios for each additional month of breastfeeding compared to never being breastfed were 0.99 (95% CI, 0.97–1.01). The adjusted odds ratios for breastfeeding durations of > 0–6 months, > 6–12 months, > 12–24 months, and > 24 months were 0.84 (95% CI, 0.51–1.36), 0.76 (95% CI, 0.42–1.35), 0.79 (95% CI, 0.43–1.45), and 0.66 (95% CI, 0.32–1.35), respectively. Compared to children who were never breastfed, the adjusted odds ratio for children who were ever breastfed was 0.79 (95% CI, 0.50–1.25). Among children with ASD, the proportion of ever breastfeeding declined from 82.0% in 2017 to 64.3% in 2020, while exclusive breastfeeding decreased from 12.0% in 2016 to 5.9% in 2020. Conclusions and relevance Although no significant association was found between infant feeding practices and ASD among US children aged 2–5 years, the rates of breastfeeding, particularly exclusive breastfeeding, were suboptimal among children with ASD. This highlights the need for specific policies and practices to promote and support breastfeeding among parents of children with ASD or those at high risk of having a child with ASD.

Abstract Objective This study aimed to evaluate the associations between particulate matter (PM), lung function and Impulse Oscillometry System (IOS) parameters in chronic obstructive pulmonary disease (COPD) patients and identity effects between different regions in Beijing, China. Methods In this retrospective study, we recruited 1348 outpatients who visited hospitals between January 2016 and December 2019. Ambient air pollutant data were obtained from the central monitoring stations nearest the participants’ residential addresses. We analyzed the effect of particulate matter with aerodynamic diameter ≤ 2.5 μm (PM2.5) exposure on lung function and IOS parameters using a multiple linear regression model, adjusting for sex, smoking history, education level, age, body mass index (BMI), mean temperature, and relative humidity . Results The results showed a relationship between PM2.5, lung function and IOS parameters. An increase of 10 µg/m3 in PM2.5 was associated with a decline of 2.083% (95% CI: −3.047 to − 1.103) in forced expiratory volume in one second /predict (FEV1%pred), a decline of 193 ml/s (95% CI: −258 to − 43) in peak expiratory flow (PEF), a decline of 0.932% (95% CI: −1.518 to − 0.342) in maximal mid-expiratory flow (MMEF); an increase of 0.732 Hz (95% CI: 0.313 to 1.148) in resonant frequency (Fres), an increase of 36 kpa/(ml/s) (95% CI: 14 to 57) in impedance at 5 Hz (Z5) and an increase of 31 kpa/(ml/s) (95% CI: 2 to 54) in respiratory impedance at 5 Hz (R5). Compared to patients in the central district, those in the southern district had lower FEV1/FVC, FEV1%pred, PEF, FEF75%, MMEF, X5, and higher Fres, Z5 and R5 (p

Abstract Background Many previous studies have reported the association between iron overload (IO) and type 2 diabetes mellitus (T2DM). However, the underlying molecular mechanism is not clear. Methods Epidemiological data from the National Health and Nutrition Examination Survey 2017–2018 (NHANES) was used to systematically explore the association between IO and diabetes. Furthermore, transcriptome data from Gene Expression Omnibus (GEO) were analyzed using bioinformatics methods to explore the underlying functional mechanisms at the molecular level. Results Data from NHANES showed a “W” shape relationship between serum iron (frozen) and the risk of diabetes (P

Abstract Bronchopulmonary dysplasia (BPD) is a chronic, devastating disease primarily occurring in premature infants. To date, intervention strategies to prevent or treat BPD are limited. We aimed to determine the effects of umbilical cord blood‐derived exosomes (UCB‐EXOs) from healthy term pregnancies on hyperoxia‐induced lung injury and to identify potential targets for BPD intervention. A mouse model of hyperoxia‐induced lung injury was created by exposing neonatal mice to hyperoxia after birth until the 14th day post birth. Age‐matched neonatal mice were exposed to normoxia as the control. Hyperoxia‐induced lung injury mice were intraperitoneally injected with UCB‐EXO or vehicle daily for 3 days, starting on day 4 post birth. Human umbilical vein endothelial cells (HUVECs) were insulted with hyperoxia to establish an in vitro model of BPD to investigate angiogenesis dysfunction. Our results showed that UCB‐EXO alleviated lung injuries in hyperoxia‐insulted mice by reducing histopathological grade and collagen contents in the lung tissues. UCB‐EXO also promoted vascular growth and increased miR‐185‐5p levels in the lungs of hyperoxia‐insulted mice. Additionally, we found that UCB‐EXO elevated miR‐185‐5p levels in HUVECs. MiR‐185‐5p overexpression inhibited cell apoptosis, whereas promoted cell migration in HUVECs exposed to hyperoxia. The luciferase reporter assay results revealed that miR‐185‐5p directly targeted cyclin‐dependent kinase 6 (CDK6), which was downregulated in the lungs of hyperoxia‐insulted mice. Together, these data suggest that UCB‐EXO from healthy term pregnancies protect against hyperoxia‐induced lung injuries via promoting neonatal pulmonary angiogenesis partially by elevating miR‐185‐5p.

Background: Patients with New York Heart Association (NYHA) grade III chronic heart failure (CHF) present with low capacity for daily activities, severe self-perceived burden, and poor quality of life. Effective nursing interventions may reduce patients’ self-perceived burden and improve their quality of life. Objectives: To explore the effects of an explain-simulate-practice-communicate-support intervention on the self-perceived burden, cardiac function, and activities of daily living (ADL) ability in patients with New York Heart Association grade III chronic heart failure. Methods: Of the 100 patients with New York Heart Association grade III chronic heart failure who were electronically randomized and equally divided into control and intervention groups, data from 88 patients who completed our study were analyzed. The primary outcome was quality of life; secondary outcomes were self-perceived burden, 6-min walking test distances, serum N-terminal pro-brain natriuretic peptide levels, New York Heart Association cardiac function classification, and ability to perform activities of daily living. Results: After 12 weeks’ intervention, the intervention group had significantly lower self-perceived burden, Minnesota Living with Heart Failure Questionnaire scores, N-terminal pro-brain natriuretic peptide levels, and New York Heart Association grades compared with the control group, while 6-min walking test distances, left ventricular ejection fraction, and modified Barthel Index scale scores were significantly higher than those in the control group (P > 0.05). Conclusions: The explain-simulate-practice-communicate-support intervention improved patients' quality of life through reducing the level of self-perceived burden, and improving cardiac function and activities of daily living ability. This intervention was found to be effective for patients with New York Heart Association grade III chronic heart failure.

IntroductionWalnut blight is a serious bacterial disease that affects the yield and quality of walnuts. Pantoea agglomerans is one of the main causative agents of walnut blight. However, there have been few studies on the response of walnuts to P. agglomerans infection.MethodsIn this study, the soluble sugar, photosynthesis, antioxidant enzyme activities, and secondary metabolites were measured, and the transcriptomic analysis was performed to determine the response of walnut tissue cultures to P. agglomerans infection.ResultsAfter pathogen inoculation, the soluble sugar content decreased, and photosynthesis was inhibited. Antioxidant enzyme (superoxide dismutase and peroxidase) activities and secondary metabolites (phenol and flavonoid) contents increased, especially in the early stages of inoculation. Transcriptomic analysis revealed that the phenylpropanoid biosynthesis pathway is induced after infection, and pathogen infection promotes ABA and ethylene signal transduction and inhibits auxin signaling. In addition, SA and JA-related gene expression was altered after inoculation with P. agglomerans, and the FLS- and calcium-mediated disease resistance signaling pathways were activated. Furthermore, our results suggested an involvement of the R-protein RPM-mediated disease resistance pathway in the response of walnuts to bacterial infections.DiscussionOur findings indicated that phenylpropanoid biosynthesis, hormone signal transduction, and plant-pathogen interaction have key roles in pathogenic inoculation, which provide insights into the molecular mechanisms in the response of walnuts to P. agglomerans infection.

Purpose: Reduced slow wave sleep (SWS) has been linked to hypertension in some studies. The aim of the study is to investigate the association between SWS and office blood pressure (BP) in non-hypertensive obstructive sleep apnea (OSA). Methods: This is a retrospective study of 3350 patients who underwent polysomnography (PSG) in our hospital. Based on quartiles of percent SWS, participants were classified into four groups. BP was measured manually on the randomly chosen arm in a seated position with sphygmomanometer after PSG in the morning, and the average of the second and third measurements was used for this analysis. Elevated office BP was defined as a systolic BP≥140 mmHg or diastolic BP≥90 mmHg. Results: There were 1365 patients with OSA and 597 primary snorers included in our study. In OSA group, OSA patients with SWS 39.2%). However, no significant relationship between decreased SWS and elevated office BP was found in primary snorers group. Conclusion: In non-hypertensive OSA patients, decreased SWS is associated with elevated office BP.

Abstract Polycyclic N-heterocycles are important structural motifs commonly found in bioactive compounds, however, their selective construction via the cyclization of allenynes remains challenging yet highly desirable. Here we show a homogeneous copper-catalyzed hetero Diels−Alder (HDA) reaction of allenynes with cis-diazenes (PTAD, 4-phenyl-1,2,4-triazoline-3,5-dione), allowing the practical and efficient synthesis of a diverse array of valuable polycyclic N-heterocycles. A temperature-controlled and stereocontrolled chemoselectivity of the reaction was observed, leading to the chemodivergent synthesis of tetracyclic pyrrolidines, pentacyclic triazepanes and tricyclic pyrrolidines. Compared with related Au-catalyzed cyclization of allenynes, this copper catalysis achieves cyclization of allenynes terminating in C–N bond formation via the HDA reaction.

Abstract Bronchopulmonary dysplasia (BPD) is characterized by abnormal development of the blood vessels and alveoli in lungs, which largely occurs in premature infants. Exosomes (EXO) from very preterm infants (VPI) with BPD (BPD-EXO) impair angiogenic activities of human umbilical vein endothelial cells (HUVECs) via EXO-miRNAs cargo. This study aimed to determine whether and how BPD-EXO affect the development of BPD in a mouse model. We showed that treating BPD mice with BPD-EXO chronically and irreversibly aggravated lung injury. BPD-EXO up-regulated 139 and down-regulated 735 genes in the mouse lung tissue. These differentially expressed genes were enriched to the MAPK pathway (e.g., Fgf9 and Cacna2d3), which is critical to angiogenesis and vascular remodeling. BPD-EXO suppressed expression of Fgf9 and Cacna2d3 in HUVECs and inhibited migration, tube formation, and increased cell apoptosis in HUVECs. These data demonstrate that BPD-EXO aggravate lung injury in BPD mice and impair lung angiogenesis, plausibly leading to adverse outcomes of VPI with BPD. These data also suggest that BPD-EXO could serve as promising targets for predicting and treating BPD.

Background: Adopting a healthy lifestyle during childhood could improve physical and mental health outcomes in adulthood and reduce relevant disease burdens. However, the lifestyles of children with mental, behavioral, and developmental disorders (MBDDs) remains under-described within the literature of public health field. This study aimed to examine adherence to 24-hour movement guidelines among children with MBDDs compared to population norms and whether these differences are affected by demographic characteristics. Methods: Data were from the 2016–2020 National Survey of Children's Health—A national, population-based, cross-sectional study. We used the data of 119,406 children aged 6–17 years, which included 38,571 participants with at least 1 MBDD and 80,835 without. Adherence to the 24-hour movement guidelines was measured using parent-reported physical activity, screen time, and sleep duration. Results: Among children with MBDDs, 20.3%, 37.0%, 60.7%, and 77.3% met the physical activity, screen time, sleep, and at least 1 of the 24-hour movement guidelines. These rates were lower than those in children without MBDDs (22.8%, 46.2%, 66.7%, and 83.4%, respectively; all p < 0.001). Children with MBDDs were less likely to meet these guidelines (odds ratio (OR) = 1.21, 95% confidence interval (95%CI): 1.13–1.30; OR = 1.37, 95%CI: 1.29–1.45; OR = 1.29, 95%CI: 1.21–1.37; OR = 1.45, 95%CI: 1.35–1.56) than children without MBDDs. Children with emotional disorders had the highest odds of not meeting these guidelines (OR = 1.43, 95%CI: 1.29–1.57; OR = 1.48, 95%CI: 1.37–1.60; OR = 1.49, 95%CI: 1.39–1.61; OR = 1.72, 95%CI: 1.57–1.88) in comparison to children with other MBDDs. Among children aged 12–17 years, the difference in proportion of meeting physical activity and screen time guidelines for children with vs. children without MBDD was larger than that among children aged 6–11 years. Furthermore, the above difference of meeting physical activity guidelines in ethnic minority children was smaller than that in white children. Conclusion: Children with MBDDs were less likely to meet individual or combined 24-hour movement guidelines than children without MBDDs. In educational and clinical settings, the primary focus should be on increasing physical activity and limiting screen time in children aged 12–17 years who have MBDDs; and specifically for white children who have MBDDs, increasing physical activity may help.

Objective: Circular RNAs (circRNAs) have been shown to participate in various cancers via sponging miRNAs (microRNAs). However, their role in lung adenocarcinoma (LUAD) remains elusive.Methods: The transcriptome data and corresponding clinical information of lung adenocarcinoma samples were extracted from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. Differentially expressed circRNAs (DEcircRNAs), differentially expressed miRNAs (DEmiRNAs), and differentially expressed genes (DEgenes) were identified and further used to constructed a circRNA-associated competing endogenous RNA (ceRNA) network. Real-Time qPCR analysis was conducted to examine gene expression at transcriptional level. The regulatory mechanisms of circRNA-miRNA-gene were validated by dual-luciferase reporter array and RNA pull-down assay. Cell growth, migration and invasion were evaluated by CCK-8 assay, colony formation assay and transwell assay, respectively.Results: Based on public microarray data, we systematically constructed a circRNA-associated ceRNA network including 11 DEcircRNAs, 8 DEmiRNAs and 49 DEgenes. Among the ceRNA network, we found that circ-0002727 was a key regulatory and was further confirmed to be upregulated in LUAD cancer cells. Subsequently, we found that silencing of circ-0002727 significantly suppressed the LUAD cell proliferation, migration and invasion in vitro. Mechanistically, we showed that circ-0002727 could competitively bind miR-144-3p to enhance the KIF14 expression in LUAD cells. Rescue assays indicated that circ-0002727 could regulate LUAD cell proliferation through modulating miR-144-3p/KIF14 pathway. Besides, KIF14 expression level was positively correlated with TNM stage and metastasis, and patients with high KIF14 expression suffered poor prognosis.Conclusion: Taken together, our study revealed that circ-0002727 could act as a ceRNA to regulate LUAD progression via modulating miR-144-3p/KIF14 pathway, providing a potential therapeutic target for LUAD.

Objective To investigate the clinical effect of Gancao Ganjiang Decoction (GGD) combined with moxibustion on the patients with end-stage renal disease (ESRD) received maintenance peritoneal dialysis (PD). Methods Sixty-two ESRD patients received maintenance PD in the First Hospital of Hebei Medical University from June 2019 to June 2021 were selected and were randomly divided into control group and treatment group (n=31, each). The routine western medicine was given in control group, while the modified GGD combined with Yiqi Huiyuan moxibustion was added in treatment group based on the routine western medicine. After 4 weeks of treatment, the TCM syndrome scores, the dialysis adequacy ［serum creatinine (Scr), blood urea nitrogen (BUN), uric acid, estimated glomerular filtration rate (eGFR),residual renal function (RRF), residual renal urea clearance index (KT/V) and PD KT/V parameters］ and the cardiac injury biomarkers ［serum amino-terminal brain natriuretic peptide (NT-proBNP), creatine kinase-myocardial band (CK-MB), cardiac troponin Ⅰ (cTnⅠ) levels］ were observed and compared between two groups. Cardiovascular adverse events were observed during 6 months follow-up period. Results After treatment, TCM syndromes scores in treatment group were statistically lower than those in control group (P

Organic molecules containing seven-membered rings are important structural motifs for drug candidates, but the construction of seven-membered rings can be challenging through traditional cyclization pathways. Here, the authors report a copper-catalyzed alkyne oxidation and Büchner-type ring-expansion to generate benzo[6,7]azepino[2,3-b]quinolines and pyridine-based diones.

Fruit firmness is an important quality trait of apple fruit texture, and the pre-harvest ripening period is the key period for the formation of apple fruit texture. Expansin is a cell wall loosing protein family that has four subfamilies: α-expansin (EXPA), β-expansin (EXPB), expansin-like A (EXLA), and expansin-like B (EXLB). In this study, we investigated the key period of pre-harvest texture formation in ‘Golden Delicious’ apples based on fruit longitudinal diameter, transverse diameter, firmness, tissue structure, respiration intensity, ethylene release rate, and expansin activity. Within the 10 days before harvest, the fruit was found to reach maturity. Semi-quantitative RT-PCR revealed that most of the expansins were expressed at the ripening stage before harvest. The biological function of the EXLB subfamily gene, MdEXLB1, was further identified, and its subcellular localization on the cell wall was confirmed by transient transformation experiments. Compared with the wild type (WT), the transgenic tomato lines overexpressing MdEXLB1 had lower plant height, earlier fruiting period, fewer days for fruit ripening, higher fruit maturity, lower fruit firmness, higher fruit expansin activity, more discrete flesh cell structure, and accelerated fruit ripening process. Overall, this is the first study to propose that the apple EXLB subfamily gene, MdEXLB1, has biological functions and plays an important role in promoting fruit ripening and softening.

The authors introduce an active-mode optical microcavity sensor with enhanced sensitivity via Förster resonant energy transfer. Changes in lasing wavelengths of both donor and acceptor enable quantitative molecular analysis and real-time monitoring of intracellular molecules.

Automatic text summarization can help people to filter and identify information quickly,grasp the key content of news,and alleviate the problem of information overload.The mainstream abstractive summarization model is mainly based on the encoder-decoder architecture.In view of the fact that the decoder does not fully consider the text topic information when predicting the target word,and the traditional Word2Vec static word vector cannot solve the polysemy problem,an automatic summarization model for Chinese short news is proposed,which integrates the BERT word embedding representation and topic information enhancing.The encoder combines unsupervised algorithm to obtain text topic information and integrates it into the attention mechanism to improve the decoding effect of the model.At the decoder side,the BERT sentence vector extracted from the BERT pre-trained language model is used as the supplementary feature to obtain more semantic information.Meanwhile,pointer mechanism is introduced to solve the problem of out of vocabulary,and coverage mechanism is used to suppress repetition effectively.Finally,in the training process,reinforcement learning method is adopted to optimize the model for non-differentiable index ROUGE to avoid exposing bias.Experimental results on two datasets of Chinese short news summarization show that the proposed model can significantly improve the ROUGE evaluation index,effectively integrate text topic information,and generate fluent and concise summaries.

Although the complete nucleotide sequence of strawberry vein banding virus (SVBV) has been determined and bioinformatic analysis has revealed that the SVBV genome could encode seven proteins, the precise function of each protein is unclear. This study provided evidence that the P1 protein of SVBV (SVBV-P1) possesses the following features. Bioinformatic and subcellular localization analyses showed that SVBV-P1 is localized in the cytoplasm and cell walls of epidermal cells in Nicotiana benthamiana, and it forms inclusion bodies associated with microtubules and the endoplasmic reticulum. Dilution experiments demonstrated that SVBV-P1 could move from the original agro-infiltrated cells to adjacent cells in N. benthamiana leaves. Further trans-complementation experiments demonstrated that SVBV-P1 could facilitate the intercellular movement of a movement-deficient potato virus X mutant in N. benthamiana leaves. Finally, yeast two-hybrid and bimolecular fluorescence complementation assays revealed that SVBV-P1 could interact with the SVBV coat protein, which is a major component of Caulimovirus virions. Results of the electrophoretic mobility shift assay indicated that SVBV-P1 lacks DNA-binding capability. In summary, the results suggest that SVBV-P1 is probably a movement protein of SVBV, providing new insights into the function of movement proteins of the Caulimovirus genus.

Ascorbate peroxidase (APX) plays a key role in scavenging reactive oxygen species (ROS) in higher plants. However, there is very little information available on the APXs in kiwifruit (Actinidia), which is an economically and nutritionally important horticultural crop with exceptionally high ascorbic acid (AsA) accumulation. This study aims to identify and characterize two cytosolic APX genes (AcAPX1 and AcAPX2) derived from A. chinensis ‘Hongyang’. The constitutive expression pattern was determined for both AcAPX1 and AcAPX2, and showed relatively higher expression abundances of AcAPX1 in leaf and AcAPX2 in root. Transcript levels of AcAPX1 and AcAPX2 were increased in kiwifruit roots treated with NaCl. Subcellular localization assays using GFP-fusion proteins in Arabidopsis protoplasts showed that both AcAPX1 and AcAPX2 are targeted to the cytosol. Recombinant AcAPX1 or AcAPX2 proteins were successfully expressed in the prokaryotic expression system and their individual ascorbate peroxidase activities were determined. Finally, constitutive over-expression of AcAPX1 or AcAPX2 could dramatically increase total AsA, glutathione level and salinity tolerance under NaCl stress in Arabidopsis thaliana. Our findings revealed that cytosolic AcAPX1/2 may play an important protective role in the responses to unfavorable environmental stimuli in kiwifruit.

Abstract Purpose The current study aimed to optimize the culture and production parameters of industrial production of lincomycin A by Streptomyces lincolnensis using a statistical approach that could also reduce unwanted by-products. Methods The Plackett-Burman design, steepest ascent method, and response surface design were used to evaluate different factors that affect lincomycin A production. Results Using an optimized S. lincolnensis fermentation medium, lincomycin A production was increased up to 4600 mg/L in shaking flasks, which indicated a 28.3% improvement over previous production in an un-optimized medium (3585 mg/L). Additionally, the concentration of lincomycin B by-product was reduced to 0.8%, which was 82.2% lower than that in the un-optimized medium. Further, quantitative real-time PCR analysis revealed the optimized medium improved lincomycin A production by stimulating key genes in the lincomycin A biosynthesis pathway, as well as an osmotic stress gene. Conclusions Based on the results, the sequential optimization strategy in this study provides powerful means for the enhancement of lincomycin A with less by-product. We found that osmotic stress reduced the concentration of lincomycin B, which could also help reduce fermentation by-product yields in other actinobacteria.

Objective To investigate the effect of sulforaphane on ischemia-reperfusion injury(I/RI) and the role of PI3K/Akt/GSK-3β pathway in heart transplantation of rats. Methods The rat model of allograft heart transplantation was established as the control group.The survival rate,the level of serum myocardial enzymes,apoptosis of myocardial cells and the swelling degree of myocardial mitochondria were compared with sulforaphane injection group (2.5 mg/kg).Western blot was used to detect the expression of apoptotic molecules caspase-3,Bax and PI3K/Akt/GSK-3β. Results The survival rate of sulforaphane group was significantly higher than that of control group(P＜0.05).The serum concentrations of LDH,CK,CK-MB and TNT in sulforaphane group were lower than those in control group with a time dependent manner at different treatment time (6,12,24 and 48 h).The expressions of caspase-3 and Bax were significantly decreased (P＜0.01),and the degree of mitochondrial swelling was also improved compared with the control group. Conclusions Sulforaphane may inhibit myocardial apoptosis by activating PI3K/Akt/GSK-3β pathway and improve I/RI after heart transplantation as shown by animal model.